The impact of SAH finding on CT to the clinical outcome after mechanical thrombectomy for large vessel occlusion.

BACKGROUND AND PURPOSE: Whether subarachnoid haemorrhage (SAH) after mechanical thrombectomy affects the clinical outcomes of patients with acute large-vessel occlusion remains unclear. This study aimed to investigate the clinical impact of SAH on computed tomography (CT) after mechanical thrombectomy. METHODS: The SKIP study was an investigator-initiated, multicentre, randomised, open-label clinical trial. This study was performed in 23 hospital networks in Japan from January 1, 2017, to July 31, 2019. Among the 204 patients, seven were excluded because they did not undergo mechanical thrombectomy (MT) and had a modified Rankin scale (mRS) score > 2. The main outcome was the association between SAH within 36 h after mechanical thrombectomy and the clinical outcome at 90 days. RESULTS: Among 197 patients, the median age was 74 (67-79) years, 62.9% were male. Moreover, 26 (13.2%) patients had SAH (seven isolated SAH) on CT within 36 h. The SAH rate did not differ according to IV rt-PA administration (p = 0.4). The rate of favourable clinical outcomes tended to be lower in patients with SAH rather than patients without SAH (11 [42%] vs. 106 [62%], p = 0.08). Among the seven patients with isolated SAH, 6 showed favourable outcomes at 90 days. In the multivariate regression analysis, the presence of SAH within 36 h from onset was not associated with clinical outcome (Odd ratio, 0.59; 95% confidence interval, 0.18-1.95; p = 0.38). CONCLUSIONS: Among patients with acute stroke treated with MT, SAH, especially isolated SAH findings on CT, were not associated with poor clinical outcomes after 90 days. TRIAL REGISTRATION NUMBER: UMIN000021488.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP.

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

Intravenous Alteplase is Associated with First Pass Effect in Stent-retriever but not ADAPT Thrombectomy : Post Hoc Analysis of the SKIP Study.

PURPOSE: To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. METHODS: This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. RESULTS: A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5-8.48) and in the ADAPT group it was 1.35 (0.37-4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37-0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. CONCLUSION: In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial.

IMPORTANCE: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. OBJECTIVE: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. INTERVENTIONS: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. RESULTS: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). CONCLUSIONS AND RELEVANCE: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000021488.

The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study).

RATIONALE: Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear. AIM: This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy. METHODS AND DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy. STUDY OUTCOME: The primary efficacy endpoint is a modified Rankin Scale score of 0-2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h. DISCUSSION: This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities. TRIAL REGISTRATION: UMIN000021488.